Health Meaning

SAN FRANCISCO -. Scientists dream of one day using a single chip studded with DNA to help determine the health risks of drugs, food additives and industrial chemicals. Now, this technique has passed a preliminary test with flying colors, the researchers reported here on March 26 at a meeting of the Society of Toxicology.

The principle is simple. The researchers exposed laboratory animals to a chemical, then extract the genetic material called mRNA (which is produced only by active genes) of their cells. A microarray chips or so-called DNA tests for the activity of thousands of genes at once. The profile of active genes should reveal exactly what the toxin is an animal -. If the signal can be distinguished from normal changes in gene activity

few months, Cynthia Afshari the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina, put the new technology to the test. Using microarrays 1,700 genes that may be important in the response of rats to toxins, the team Ashfari first product of genomic fingerprint for two types of liver toxins well studied: phenobarbital and three members of a diversified chemical class of compounds called peroxisome proliferators. Then they did a blind test of rat mRNA from another laboratory.

By comparing gene activity in these 26 extracts the two references, postdoc Hisham Hamadeh of Ashfari correctly identified all the rats that had been exposed to a peroxisome proliferator or phenobarbital derivative. He also acknowledged that several rats were exposed to a wild-card consists not in the database. Hamadeh made only one mistake, misidentification of a wild-card sample as a weak analog of phenobarbital; it was actually an unrelated compound.

The accuracy of DNA matrix surprised scientists who filled the room for the presentation of Afshari. "This work is important," said J. Christopher Corton, the CIIT Centers for Health Research in Research Triangle Park, North Carolina. Toxicologists have a long way to go before they can use genomic tests to predict a wide range of toxicities, he added. But the work of Afshari shows that the objective can be achieved much more quickly than expected, Corton said.

Related Sites

Summary of presentation
home of Cynthia Afshari Page

AIDS not only causes immense human suffering, it is also a significant financial burden. The cost of prevention and care in the developing world will more than quadrupled to $ 9.2 billion annually by 05, according to an international group of experts. The report, published online June 22 by Science , was designed to guide discussions at a special session on HIV / AIDS of the General Assembly of the United Nations this week. "We wanted to give people [numbers] to work with," says economist Lori Bollinger Futures Group International in Glastonbury, Connecticut.

Omit the developed world, where the cost of AIDS is not a major issue, the Panel reviewed 135 nations, including low-income countries in sub-Saharan Africa and in middle-income countries like Brazil and Thailand. They estimated that about $ 4.8 billion will be needed to reduce the rate of infection While prevention programs such as the reduction of mother to child transmission and distribution of condoms. Adequate care and support for those infected, including supervision of orphans, will add $ 4.4 billion more. The study does not include funds to develop new drugs and vaccines.

So where should the money come from? The authors note that as of now, the countries studied are spending $ 1.8 billion annually on HIV / AIDS. To offset the shortfall, they suggest that a third to half of the money could come from local sources such as government, private sector and individual donations, with foreign funds, which make up the rest. But the ability of countries to pay will be different, the panel said sub-Saharan Africa and parts of Asia, up to 80% may come from abroad, while countries like Brazil could pay 0% bill themselves [

"it was the first analysis that really got us pretty close to what the actual expenditure," says tropical medicine expert Paul de Lay the uS Agency for International development in Washington, DC from the main weakness of the study, he notes, is that it ignores the additional costs for basic infrastructure, such as building hospitals and training people. Although difficult to assess, these factors could add billions more to the bottom line, Lay said.

Related site

The Joint United Nations Programme on HIV / AIDS

Like all animal tissues, cancerous tumors need blood to survive, and one of the hottest areas of research cancer is to find ways to block the blood supply. Now scientists have created a new treatment that destroys blood vessels supplying tumors in mice while leaving others unscathed blood vessels. Scientists say the findings could eventually lead to new therapies against cancer in humans.

Cancer researchers have high hopes when scientists reported in 1997 that two new drugs, angiostatin and endostatin, prevented the growth of blood vessels and dramatically reduced in tumors mouse. Many of these so-called anti-angiogenesis drugs are in clinical trials, and early results look promising. But these drugs all have one major drawback: Although they stop or slow tumor growth, they do not destroy existing blood vessels of the tumor. This should be possible because the inner walls of tumor vessels are covered with a protein called tissue factor (TF) not present in normal blood vessels.

biochemists from the University Yale Zhiwei Hu and Alan Garen exploited this difference to create a new drug that seeks blood vessels of the tumor and destroys them. The drug, known as Icon is a unique compound consisting of two parts, which recognizes the blood vessels coated with TF and another that causes the immune system to attack them. The researchers speculated that these two components together should attack the tumor vessels without harming normal ones. To test icon, they injected a virus genetically designed to produce seven mice with cancer of the human prostate.

In the early edition of the October 2 Proceedings of the National Academy of Sciences , they report that tumors in mice decreased steadily for about 0 days with only a small sliver remaining at the end of the experiment. In contrast, tumors in the seven control mice grew rapidly and they died within 63 days. The treatment was effective against human melanoma tumors in mice as well, and scientists believe it may struggle against a range of cancers.

Harvard biologist Cancer Judah Folkman, who studies the anti-angiogenesis drugs, said "the novel researchers and elegant approach" may lead to new therapies that can be tested for human cancers. "This is a very important document," says Folkman.

Related Sites

homepage Alan Garen
Angiogenesis Foundation

Researchers have discovered how HIV can penetrate the tight nucleus of an infected cell, a necessary step for the virus to replicate. Somehow, the virus sabotages the nuclear membrane with numerous punctures. The discovery could provide a new target for future drugs against AIDS.

The HIV (HIV) breeds entering the nucleus of a cell and supported. Once inside, copies of HIV DNA in its genome RNA, which slips into the cell's DNA. Then, when the cell prepares to divide, it copies inadvertently viral genome into RNA, the model for the manufacture of proteins. These proteins then assembled into new HIV particles which can infect other cells. To make more than one copy, the virus uses a protein called Vpr which stops the cell from normal cell division cycle. As a record skipping, the cell can not progress in the division, but the viral genome transcribed into RNA, again and again.

virologist Warner Greene and colleagues at the University of California, San Francisco, and Northwestern University Medical School, wanted to know how the virus stops the cell cycle. The team used video fluorescence microscopy to track the movement of proteins related to cell cycle-in and out of the cell nuclei, watch how traffic varies with the presence of Vpr. "I am astonished," said Greene. Vpr was present when the buttons appeared on the membrane surrounding the nucleus. Some curved until they burst, breaking the seal between the cytoplasm and the nucleus by an unknown mechanism. Reporting in the Nov. 2 issue of Science , the team suggests that these offenses can give HIV easy access to the nucleus. Normally, it is too large to pass through the membrane.

The conclusion only increases the respect of researchers for HIV. "It's blowing holes in the nuclear envelope, and it is just as radical as you can get," says cell biologist Katherine Wilson of the Johns Hopkins University School of Medicine. Wilson said the finding may encourage drug designers to consider Vpr as a potential antiviral target. "It is an important document," she said, "because it's making us look in a new direction."

Related Sites

Videos of Science article
Greene laboratory homepage
Wilson Homepage laboratory

CHICAGO - While thousands enter the new year sneezing and coughing winter colds, a company pharmaceutical said it might have something to offer. A new antiviral drug shortens the course of colds by one day, according to results of a clinical trial large Phase III published here on December 17 at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Americans spend $ 3.5 billion annually remedies against colds, which target only the symptoms. The new drug, pleconaril, attack instead of a group of viruses called rhinoviruses, which cause about half of all colds. Jointly developed by ViroPharma Inc. of Exton, Pennsylvania, and Aventis Pharmaceuticals, based in Strasbourg, France, PLECONARIL acts like a molecular glue, preventing rhinoviruses that erupted in the cells to release their genes to copy.

To test how cold the drug controls in adults, Frederick Hayden of the University of Virginia School of Medicine have coordinated a clinical trial of 2,096 adults across the United States and Canada who had moderate to severe runny nose and at least one other symptom, such as a sore throat, nasal congestion, cough, muscle aches, or general malaise. Patients were randomized to receive either the drug or a placebo and took the pills until their runny had relaxed for 2 days.

self rating patient revealed that it took 2.9 days until their symptoms were half as severe as on the first day, compared to 3.9 days for the placebo group . The second day of the cold, the rhinovirus can be cultured from nasal mucus samples in 85% of placebo patients, but only 60% of patients taking the drug. ViroPharma, which funded the study, is also the pleconaril trial on children with colds and try to determine whether the drug can completely prevent the common cold, said Mark McKinlay, vice president of research and society development.

Although drug shortens the disease in just a day or two, "you can not expect much more with a disease that is measured in days," says virologist Scott Hammer of Columbia University. If the Food and drug Administration approves peconaril, the drug could be on the market in autumn 02. - in time for the fight winter colds of next year

Related Sites

ongoing trials of ViroPharma pleconaril
Facts about colds

CAMBRIDGE, UK - For survivors of the atomic bombs on Japan fell at the end of the Second World War, burns and disfiguring diseases radiation-induced were too real and scary. Now researchers have a strong new evidence of a more insidious effect in others blighted by nuclear weapons :. Unexplained DNA mutations atomic tests in Kazakhstan in the early days of the Cold War

As indicated in Science , Yuri Dubrova and colleagues at the University of Leicester, UK the blood collected from three generations of 40 families in the district Beskaragai Kazakhstan, a desert region particularly affected by four surface atomic tests between 1949 and 1956. the researchers examined DNA minisatellite subjects - short repetitive sequences pepper genome. In each subject they examined eight minisatellite DNA regions that are prone to mutations. The mutation rate naturally rich in this DNA enables researchers to detect statistically significant increases in mutation rates in small populations.

When the data returned, "I could not believe my eyes," says Dubrova. As compared to control families in a non-irradiated part of Kazakhstan, people exposed to radioactive fallout had a rate of transfer about 80% higher, and their children showed an average increase of 50% over Sonder, Dubrova's group found an effect related to the apparent dose in children. - proof that the radiation, not a another environmental factor, induced mutations

These findings challenge the conventional view that the radiation inflicts his punishment. DNA only by direct corruption of nucleic acids, said Dudley Goodhead, director of Genome stability Unit . radiation Medical Research Council UK and Harwell Goodhead indicates that the mutation rate found in Kazakhstan is "too large magnitudes" to be counted by direct damage to the DNA of the germ line - DNA that is passed from parent to child. But exactly how long-term exposure to low-dose radiation leads to a high rate of mutation is unknown.

What these changes mean for germline health is a mystery, said Bryn Bridges of Cell Mutation Unit Medical Research Council in Brighton, UK. But evidence is mounting that Minisatellites affect gene transcription and hiking the risk of contracting certain diseases. Screening for these mutations may offer a new tool for radiation exposure monitoring, says William Morgan, director of the Research Laboratory of Radiation Oncology at the University of Maryland School of Medicine in Baltimore.

Related Sites
homepage of Dubrova
Information on nuclear testing in Kazakhstan Development Gateway Kazakhstan

Scientists use own red blood cells of a patient to deliver needed drugs directly to cells in the body. A new test of the art suggests that effectively delivers steroids in the lungs of patients with cystic fibrosis; In addition, a single dose lasts for at least a month. In the long term, scientists hope the technique could also be applied for uses as diverse as gene therapy and HIV treatments.

Many treatments, such as modified genes and new drugs are too heavy to cross cell membranes and do their job. Mauro Magnani and colleagues at the University of Urbino, Italy, wanted to overcome this problem. To do this, immersed blood cells in saline. Differences in osmotic pressure between the solution inside of the elongated cells in the pores in the cell membranes, allowing large molecules to be pressed. When the cells were removed from the solution, they chewed their usual size with the medicament sealed within. A pilot study found that cells released the steroid dexamethasone in the blood of patients with chronic obstructive pulmonary disease, and remained in the circulating blood for 7 days.

Now, a second study found similar success with cystic fibrosis. In the June issue of Gene Therapy , Magnani's team reports that this method of delivery offers dexamethasone, which is also used to treat this disease, for the blood of patients for 1 month. In both studies the drug was sealed in RBCs of patients in an inactive form, before being decomposed by enzymes in the cell to a size that may leak into the blood. Magnani believes that the technique has far-reaching applications. Red blood cells can carry new compounds such as modified genes and cells can also be modified to attract specific immune cells that may harbor germs such as HIV and tuberculosis.

"There is a great strategy," says biochemist Philip Low, Purdue University in West Lafayette, Indiana. "He should certainly be able to achieve the [cache] virus that is not accessible to conventional therapy. "

Related Sites
The homepage of Philip Low
NIH brochure cystic fibrosis

A small molecule blowing power plants tumor cells but leaves normal cells unharmed may provide a model for new drugs against cancer. The molecule is drawn to the unique electrical properties of mitochondria energy production in tumor cells, and once ensconced, kick off a series of events leading to cell suicide.

Best known for his role as power generators cells, mitochondria also influence whether a cell lives or dies. When stressed, mitochondria rupture or leak, factors that activate enzymes that release dismantle the entire cell. This process is called apoptosis. A molecule that jumps-starts apoptosis in tumor cells - and only the cells - could be a useful drug against cancer

The researchers led by geneticist Valeria Fantin from Harvard Medical School in Boston screened more 16,000 small molecules. see if were taken selectively by the tumor cells. A molecule called F16 has passed the test. The reason, says Fantin is that F16 has a positive charge and is drawn into the mitochondria of cancer cells, the inner compartments are charged more negatively than in normal cells. More importantly, once in the mitochondria, F16 triggers apoptosis, the team of Fantin reports in the July 15 issue of Cancer Cell .

One potential drawback, noted molecular geneticist Andreas Strasser Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, is that F16 can damage normal cells with high metabolic activity. In the absence of in vivo data critical to the safety of this compound, it can not be considered a promising cancer drug, he said. Even so, the study may renew interest in the therapeutic potential of this class of molecules (delocalized lipophilic cations), say Yardin Yosef, a molecular biologist at the Weizmann Institute of Science, and Chausovsky Alexander, vice president of research Zetiq Technologies in Rehovot, Israel.

related sites
Councillor site of Fantin
Background on apoptosis and cancer chemotherapy
More on apoptosis

DENVER -. There are over 2 decades, the United States began to eliminate lead additives in gasoline and paint. But new research suggests that many children living in large cities are still at risk of lingering lead in soil. Study finds contaminated soil in Indianapolis is correlated with elevated blood lead levels in children, and other cities are likely to have similar problems.

In the 1970s lead poisoning has been identified as a serious threat to children, causing disorder behaviors, permanent drop in IQ, paralysis and even death. Children are more vulnerable because, before the age of six, they absorb about 80% of all the lead they ingest, while adults absorb about 15%. These revelations have spurred legislation to reduce lead exposure, but an important source of lead may have been overlooked, said geochemist Gabriel Filippelli at Indiana University-Purdue Indianapolis (IUPUI).

Filippelli and graduate student Mark Laidlaw tested some 100 samples of surface soil of the world Indianapolis and found that high levels of lead were omnipresent. Lead in the soil is left on auto emissions before unleaded gasoline was said Filippelli. Not surprisingly, the levels are higher near busy roads, but water and wind have spread more slowly. He then compared the levels of soil with lead levels in the blood recordings in children of public health. "There is a halo of high levels of lead around the city, and is linked particularly to the lead levels in the blood of children," he said. Filippelli reported the results of his study this week at the meeting of the Geological Society of America.

lead risks in the soil have been neglected, said Filippelli. The children come into contact with lead in playgrounds and even their own backyards, and follow in their homes, he said. This could explain why high levels of lead in the blood have been found in children living in brick houses, which tend to have some paint, and do not play near roads.

"We thought we had solved the problem when we took the lead in gasoline," said environmental toxicologist Howard Mielke of Xavier University in New Orleans, which found lead levels Similar to other cities. "The good news is the problem is solvable," he said. The new study found that 95% of the lead was in the top 13 centimeters of soil to remove the top layer of soil in areas where children play would go a long way toward reducing exposure.

Related Sites
IUPUI lab biogeochemistry
information on lead poisoning, the National Library of Medicine

The devastating Ebola virus might be able to steal a victim to another, speculate scientists have confirmed a link between Ebola and bird viruses. The results suggest that the Ebola virus has evolved from the same ancestor as bird retroviruses, raising the possibility that the birds could still be carriers. However, the same research also has a good side :. A mutant version of an Ebola protein could lead to a promising new vector for gene therapy

biochemist David Sanders of Purdue University in West Lafayette, Indiana, and co workers made the discovery while studying a glycoprotein molecule on the surface of the virus that allows it to break into the host cells. The team used a variety of biochemical techniques to determine the structure of the glycoprotein and study the complex sequence of changes that the virus makes to the glycoprotein entering cells.

The Ebola glycoprotein appears to be very similar to the structure and function of glycoproteins found in some bird retroviruses, the team reports in the December 15 issue of Journal of Virology . The possibility of a common evolutionary past is very strong, says Sanders. But he is quick to warn that the natural host of the Ebola virus is unknown, and epidemiological studies are needed to determine if birds are involved.

The team also found a way to put the Ebola potentially beneficial use. A mutated version of the virus that has failed a particular region of the glycoprotein was much more effective to penetrate into the cells, making it a promising candidate for use in gene therapy. Ebola is one of the few viruses that attack the lungs directly from respiratory tract rather than in the bloodstream; thus, the shell could be used to create an inhalation treatment. Sanders is considering the combination of the shell of an Ebola virus with the mutated virus glycoprotein with a second, less deadly that would provide the genetic information needed to address diseases such as lung cancer or cystic fibrosis.

Previous genetic evidence pointed to a similarity between Ebola and bird retroviruses, says molecular geneticist Paul McCray from the University of Iowa in Iowa City, but "it is a fascinating link to say that they are related in terms of evolution. "the mutant protein is another exciting product research, he added.

Related Sites
David Sanders website
information Ebola Centers for Disease Control and Prevention
information filoviruses, the category that includes Ebola